患者的临床药理学:选择性cyclo-oxygenase-2抑制剂。

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崔Rordorf厘米,L,马歇尔P, Mangold简森-巴顿

患者的临床药理学:选择性cyclo-oxygenase-2抑制剂。

Pharmacokinet。2005; 44 (12): 1247 - 66。doi: 10.2165 / 00003088-200544120-00004。

PubMed ID

16372823 (在PubMed

]

文摘

患者(Prexige)是一种选择性cyclo-oxygenase (COX) 2抑制剂用于治疗骨关节炎、类风湿性关节炎和急性疼痛。患者具有羧酸集团使其弱酸性(酸离解常数(pKa) 4.7),区分从其他选择性cox - 2抑制剂。患者具有良好的口服生物利用度(74%)。快速吸收,达到最大血浆浓度给药后2小时,血浆蛋白结合的。从等离子体的患者有一个消除半衰期短(平均4小时)和演示dose-proportional等离子体药物动力学多次给药期间没有积累。类风湿性关节炎患者,峰值的患者滑液浓度比等离子体发生3 - 4小时后从5小时后超过血浆浓度和剂量的最后24小时给药间隔。这些数据表明,患者可能会降低系统性风险,同时还达到地点cox - 2抑制需要缓解疼痛。患者之前广泛代谢排泄,只有少量尿液或粪便排泄不变。患者及其代谢物通过肾脏排泄,粪便大约等量的路线。的主要代谢途径识别涉及氧化5-methyl组患者和/或羟基化的dihaloaromatic戒指。 Major metabolites of lumiracoxib in plasma are the 5-carboxy, 4'-hydroxy and 4'-hydroxy-5-carboxy derivatives, of which only the 4'-hydroxy derivative is active and COX-2 selective. In vitro, the major oxidative pathways are catalysed primarily by cytochrome P450 (CYP) 2C9 with very minor contribution from CYP1A2 and CYP2C19. However, in patients genotyped as poor CYP2C9 metabolisers, exposure to lumiracoxib (area under the plasma concentration-time curve) is not significantly increased compared with control subjects, indicating no requirement for adjustment of lumiracoxib dose in these subjects. Lumiracoxib is selective for COX-2 compared with COX-1 in the human whole blood assay with a ratio of 515 : 1 in healthy subjects and in patients with osteoarthritis or rheumatoid arthritis. COX-2 selectivity was confirmed by a lack of inhibition of arachidonic acid and collagen-induced platelet aggregation. COX-2 selectivity of lumiracoxib is associated with a reduced incidence of gastroduodenal erosions compared with naproxen and a lack of effect on both small and large bowel permeability. Lumiracoxib does not exhibit any clinically meaningful interactions with a range of commonly used medications including aspirin (acetylsalicylic acid), fluconazole, an ethinylestradiol- and levonorgestrel-containing oral contraceptive, omeprazole, the antacid Maalox, methotrexate and warfarin (although, as in common practice, routine monitoring of coagulation is recommended when lumiracoxib is co-administered with warfarin). As such, dose adjustments are not required when co-administering these agents with lumiracoxib. In addition, moderate hepatic impairment and mild to moderate renal impairment do not appear to influence lumiracoxib exposure.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
的患者	细胞色素P450 1 a2	蛋白质	人类	未知的	底物	细节
的患者	细胞色素P450 2 c19	蛋白质	人类	未知的	底物	细节
的患者	细胞色素P450 2 c9	蛋白质	人类	未知的	底物	细节